AM-6494   Click here for help

GtoPdb Ligand ID: 10520

Synonyms: compound 20 [PMID: 31589043]
PDB Ligand
Compound class: Synthetic organic
Comment: AM-6494 is a beta-secretase 1 (BACE1) inhibitor that has been demonstrated oral efficacy in reducing central Aβ40 load in in vivo models [1]. It has been advanced to preclinical evaluation.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 137.02
Molecular weight 473.13
XLogP 1.87
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES C#CCOc1ncc(nc1)C(=O)Nc1cc(F)c(c(c1)C1(C)N=C(N)SC2(C1C2)COC)F
Isomeric SMILES C#CCOc1ncc(nc1)C(=O)Nc1cc(F)c(c(c1)[C@@]1(C)N=C(N)S[C@@]2([C@H]1C2)COC)F
InChI InChI=1S/C22H21F2N5O3S/c1-4-5-32-17-10-26-15(9-27-17)19(30)28-12-6-13(18(24)14(23)7-12)21(2)16-8-22(16,11-31-3)33-20(25)29-21/h1,6-7,9-10,16H,5,8,11H2,2-3H3,(H2,25,29)(H,28,30)/t16-,21+,22+/m0/s1
InChI Key IPUJINDWAGRAHN-KNXBSLHKSA-N
Bioactivity Comments
AM-6494 reduces CSF and brain levels of Aβ40 in rat and monkey pharmacodynamic models [1]. It is devoid of inhibitory activity against cathepsin D. AM-6494 did not cause skin/fur hypopigmentation in a mouse model, which is indicative of its BACE2-sparing activity profile.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
beta-secretase 1 Mm Inhibitor Inhibition 9.4 pIC50 - 1
pIC50 9.4 (IC50 3.6x10-10 M) [1]
beta-secretase 1 Hs Inhibitor Inhibition 9.4 pIC50 - 1
pIC50 9.4 (IC50 4x10-10 M) [1]
beta-secretase 1 Rn Inhibitor Inhibition 9.2 pIC50 - 1
pIC50 9.2 (IC50 6.2x10-10 M) [1]
beta-secretase 2 Hs Inhibitor Inhibition 7.7 pIC50 - 1
pIC50 7.7 (IC50 1.86x10-8 M) [1]